In the first 3-year phase of this comprehensive analysis of the corneal environment, the pH characteristics of over 2400 human tear samples have now been measured using a closed chamber, temperature regulated micro-electrode system. To date, the following studies have been completed: (1) A quantitative analysis of individual diurnal variations, and the development of composite models of such patterns; (2) An investigation of the effects of prolonged eye closure on tear pH; (3) The development of a pH challenge test for quantifying the buffer capacity of human tears; (4) A survey of incremental responsiveness of human tears to a spectrum of alkali strengths; and (5) A longitudinal study of the effect of contact lenses (as for aphakic or therapeutic purposes) on human tears throughout the adaptation process. Now being completed are studies on (1) The effects of incremental pH steps on corneal oxygen uptake (animal models); (2) The impacts of specific transients (e.g., blink frequency, tear evaporation rates, temperature, relative humidity and specific gas mixtures (O2, N2, CO2) on pH functions); and (3) Determination of the pKa value for tears. This second 3-year phase of study of the corneal environment will be directed toward tear osmolality. A new nanoliter volume method will be applied to follow up a previously completed larger volume (microliter) pilot survey of human tear osmolality. Nanoliter sampling will now make possible: (1) Refined quantitative analyses of location differences within an eye; (2) More accurate comparative studies of basic verses reflex tears; (3) The dynamic tracking of osmotic patterns in an eye by time lapse mapping of local sites; and (4) Improved accuracy in monitoring the effects of various transients (e.g., blink rate, temperature, relative humidity) on tear osmolality; and (5) The more precise correlation of corneal responsiveness to such factors, pachometrically and by standard clinical methods. The long-term objectives of this project remain: To quantitatively measure and analyze through frequent small volume sampling, the physiological nature and variations of the corneal environment in order to develop more accurate physiological baselines against which pathological disturbances might be better gauged, ophthalmic pharmaceuticals more effectively formulated and therapeutic bandage lenses better designed.